Maternal Hepatic Growth Response to Pregnancy in the Mouse

Abstract

Pregnancy is characterized by physiological adjustments in the maternal compartment. In this investigation, the influence of pregnancy on maternal liver was examined in CD-1 mice. Dramatic changes were observed in the size of the maternal liver during pregnancy. Livers doubled in weight from the nonpregnant state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a physiological event of liver growth confirmed by DNA content increase and detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was initiated following implantation and peaked at parturition. The expression and/or activities of key genes known to regulate liver regeneration, a phenomenon of liver growth compensatory to liver mass loss, were investigated. The results showed that pregnancy-dependent liver growth was associated with IL-6, TNF1α, NFkB, c-Jun, and IL-1β, but independent of HGF, FGF1, TNFR1, CAR, and PXR. Furthermore, maternal liver growth was associated with the activation of hepatic STAT3, β-catenin, and EGFR, but pregnancy did not activate hepatic c-Met. The findings suggest that the molecular mechanisms regulating pregnancy-induced liver growth and injury-induced liver regeneration exhibit overlapping features but are not identical. In summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic growth response driven by hepatocyte proliferation and size increase. Remarkably, our findings provide a novel mouse model to investigate the regulation of hepatocyte proliferation, cell size increase, and liver growth.

Prolactin promotes normal liver growth, survival, and regeneration in rodents: effects on hepatic IL-6, suppressor of cytokine signaling-3, and angiogenesis

“…Indeed, studies in rats show that LBW is high in nursing pups during lactation (18) when they are being exposed to high levels of PRL in milk (46). Moreover, the PRLR is upregulated in the pregnant liver (23), and hyperprolactinemia associates with liver enlargement during pregnancy and lactation (3,15,27). PRL also influences early events of liver regeneration leading to animal survival and hepatic growth.…”

“…In rodents, hepatocyte replication peaks during the first 2 wk of age (18), doubles during pregnancy (15), and continues to increase throughout lactation (27). Pathological conditions such as toxic injury and infection trigger hepatocyte proliferation to replace damaged tissue (17).…”

Influence of pregnancy in mid-to-late gestation on circulating metabolites, visceral organ mass, and abundance of proteins relating to energy metabolism in mature beef cows1,2

“…Baldwin et al (1980) suggested that identifying animals that can minimize mass of high energy demanding tissues, such as the liver, more independent of nutrient intake, may reduce apparent maintenance requirements by 10 to 30%. Previous research has shown that visceral organ mass can be influenced by both pregnancy and nutrient intake in pregnant sheep (Fell et al, 1972;Scheaffer et al, 2004;Caton et al, 2009), beef cows (Meyer et al, 2010), and in rodents (Dai et al, 2011).…”

Differential expression of T helper cytokines in the liver during early pregnancy in sheep

“…It has been reported that IL-10 plays a role in regulating placental development and foetal programming, and IL-10 knockout results in increases in the foetal weight and placental size in IL-10 null mutant mice (Roberts et al, 2003). In order to adapt the demands of pregnancy, there exists maternal hepatic growth, including hepatocyte proliferation and size increase in mice (Dai et al, 2011;Wang et al, 2015). It is supposed that the hepatocyte proliferation and size increase may be related with the decrease in IL-10.…”